A Computational Model For Nanoparticle Delivery Across Lymphatics

Abstract

In order to increase the efficacy and reduce the side effects of immunotherapies, immune-modulating drugs should be delivered directly to secondary lymphoid organs, such as lymph nodes, where a majority of immune cells reside. Nanoparticle drug delivery systems are increasingly being used for therapeutic applications, since the size of the particles allows them to effectively extravasate into the lymphatic system. Besides size, surface properties also affect the ability of nanoparticles to accumulate in lymph nodes. Due to the complex nature of the fundamental mechanisms underlying lymphatic transport, computational models for drug delivery are a valuable tool. Computational models allow us to elucidate the mechanisms behind transport, as well as observe the effects of various properties of the drug delivery vehicle on its transport. Here, an artificial neural network based computational model was used to correlate nanocarrier surface properties with increased transport efficacy. Neutral, hydrophilic surface chemistry achieved through coating of nanoparticles with polyethylene glycol was found to be optimal. This knowledge will inform nanoparticle design, which will be vital to improving the delivery, and therefore efficacy, of immunotherapies.